Condition category
Musculoskeletal Diseases
Date applied
16/05/2011
Date assigned
22/06/2011
Last edited
04/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Stuart Ralston

ORCID ID

Contact details

University of Edinburgh
Institute of Genetics & Molecular Medicine
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

19403

Study information

Scientific title

Fractures and Bisphosphonates: a double-blind, randomised controlled trial on the effect of alendronic acid on healing and clinical outcomes in wrist fractures

Acronym

FaB

Study hypothesis

Bisphosphonates are widely used in the treatment of osteoporosis. Although fractures often occur in patients with osteoporosis who are on bisphosphonate therapy, the effects of bisphosphonates on fracture healing have not been adequately studied in humans.
Sometimes bisphosphonates are withheld because of the theoretical concern about an adverse effect on fracture healing, but sometimes bisphosphonate therapy is continued. It remains unclear whether early treatment might be advantageous or deleterious to fracture healing and clinical outcome.

This study will investigate the effect of alendronic acid on radiological fracture healing in the context of a randomised placebo controlled trial. Patients aged 50 and over who have fractured their wrist and are not on bisphosphonate therapy will be invited to take part in the study.

Ethics approval

Fife and Forth Valley REC, 03/08/2011

Study design

Double-blind randomised controlled multicentre study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Fracture healing

Intervention

1. Participants are allocated to receive either 70mg alendronic acid or placebo once-weekly for 24 weeks
2. It will be compared against a matched placebo
3. Participants will take study medication for 24 weeks

Intervention type

Drug

Phase

Not Applicable

Drug names

Alendronic acid

Primary outcome measures

1. Comparing the fracture healing between both arms at 4 weeks using X-rays
2. Fractures will be defined as healed when the following features are present:
2.1. Bridging of three out of four cortices
2.2. Radiographic evidence of endosteal healing
2.3. Organised trabecular bridging
3. Also, a time to event analysis will also be performed to evaluate the trajectory of fracture healing from radiographs taken at 2, 4, 6 and 8 weeks.

Secondary outcome measures

1. Upper limb function will be assessed by using the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome Measure
2. The DASH is a validated 30-item questionnaire which has previously been shown to detect changes of disability over time after injury or surgery in patients with upper-extremity musculoskeletal disorders
3. The effect of alendronate on the DASH score during the trial will be measured by comparing the change in DASH score from initial fracture to each timepoint (baseline, 2, 4, 6, 8 and 26 weeks) for both treatment groups
4. Complex Regional Pain Syndrome type I will be assessed at weeks 6 and 26 using the clinical Budapest Criteria
5. Pain will be assessed using an 11 point (0-10) Numeric Rating Scale (NRS) and by recording the amount of analgesia used in the 24 hours prior to questioning
6. Participants will be asked rank their pain from 0 (no pain) to 10 (worst pain imaginable) 7. The difference in pain and analgesia use at baseline, weeks 2, 4, 6, 8, and 26 will be compared between both treatment groups
8. Active range of movement (AROM) and grip strength of both the affected and unaffected hand will be measured at weeks 8 and 26, using a goniometer and hand dynamometer respectively
9. The differences between the range of movement and grip strength in each hand will be used to compare the two treatment groups

Overall trial start date

30/09/2011

Overall trial end date

29/09/2013

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 19/09/2012:
1. Patients (male and female) aged 50 years and over
2. Patients must have suffered a distal radial fracture confirmed by X-ray radiograph
3. The distal radial fracture must be:
3.1. Unilateral extra-articular or minimal articular
3.2. Displaced or un-displaced
3.3. Treated with cast/splint, external fixation or open reduction and internal fixation
4. Patients willing and able to consent and comply with study protocol

Previous inclusion criteria until 19/09/2012:
3.3. Treated with cast, external fixation or open reduction and internal fixation

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

500

Participant exclusion criteria

Current exclusion criteria as of 19/09/2012:
1. Any of the following:
1.1. current or previous use of zoledronic acid
1.2. current or previous use within the last 2 years of any other bisphosphonate
1.3. current or previous use within the last 6 months of strontium ranelate, calcitonin, denosumab, parathyroid hormone (PTH) or intravenous (IV), intramuscular (IM) and oral corticosteroids (inhaled corticosteroids such as asthma inhalers are acceptable)
2. Previous distal radial fracture on affected side
3. Bilateral distal radial fracture
4. Contraindications to alendronic acid, including but not limited to:
4.1. Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achlasia
4.2. Inability to stand or sit upright for at least 30 minutes
4.3. Hypersensitivity to alendronate or any of its excipients
4.4. Known hypocalcaemia
4.5. Known renal impairment
5. Women of childbearing potential not using adequate contraception
6. Pregnancy
7. The distal radial fracture is due to other pathologies e.g. Paget’s Disease of Bone, metastatic bone disease etc.

Previous exclusion criteria until 19/09/2012:
1. Any of the following:
1.1. Current or previous use of zoledronic acid
1.2. Current or previous use within the last 2 years of any other bisphosphonate
1.3. Current or previous use within the last 6 months of strontium ranelate, calcitonin, denosumab, parathyroid hormone (PTH) or intravenous (IV), intramuscular (IM) and oral corticosteroids (inhaled corticosteroids such as asthma inhalers are acceptable)
2. Previous distal radial fracture on affected side
3. Bilateral distal radial fracture
4. Contraindications to alendronic acid, including but not limited to:
4.1. Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achlasia
4.2. Inability to stand or sit upright for at least 30 minutes
4.3. Hypersensitivity to alendronate or any of its excipients
4.4. Hypocalcaemia at baseline (serum adjusted calcium <2.2mmol/l)
4.5. Renal impairment at baseline [estimated glomerular filtration rate (eGFR) less than 35ml/min as assessed by the Modification of Diet in Renal Disease (MDRD) formula]
5. Women of childbearing potential not using adequate contraception
6. Pregnancy

Recruitment start date

02/04/2012

Recruitment end date

29/09/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Edinburgh
Edinburgh
EH4 2XU
United Kingdom

Sponsor information

Organisation

University of Edinburgh (UK)

Sponsor details

Academic and Clinical Central Office for Research and Development (ACCORD)
Research & Development Management Suite
The Queen’s Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

Sponsor type

University/education

Website

http://www.accord.ed.ac.uk/

Funders

Funder type

Charity

Funder name

Arthritis Research UK (UK) (ref no 19403)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

04/04/2016: No publications found, verifying study status with principal investigator